Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care

Sedation Complication Clinical Trial

Official title:

Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05371886
• Other study ID #: PHARAONIC
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2023
• Est. completion date: July 1, 2025

Study information

• Verified date: March 2024
• Source: Centre Hospitalier Intercommunal Creteil
• Contact: Manon TAUZIN, MD
• Phone: 01 45 17 50 00
• Email: manon.tauzin[@]chicreteil.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to describe a dose-effect relationship of morphine alone and morphine and midazolam administered as continuous infusion in neonates hospitalized in Neonatal intensive care unit and undergoing mechanical ventilation, through PKPD modelling.

Description:

This study will include all neonates receiving a sedo-analgesia with continuous infusion of morphine alone or morphine and midazolam during mechanical ventilation in 3 French NICUs. Comfort and pain will be assessed by COMFORTneo pain scores and Newborn Infant Parasympathetic Evaluation Index. Morphine, midazolam and their metabolites' concentrations will be determined on samples taken during a planned blood test. Through PKPD modelling, the dose-concentration-effect relationships will be found and interindividual variability of these drugs in neonates and simulate doses needed to achieve comfort in neonates according to their individual characteristics (gestational age, post-natal age, weight etc.).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Weeks to 45 Weeks

Eligibility

Inclusion Criteria:

• Neonates < 45 weeks of corrected gestational age

• Hospitalized in a Neonatal Intensive Care Unit

• Undergoing mechanical ventilation

• Patients that receive morphine alone or morphine and midazolam as continuous infusion

• Affiliated to a social security system

Exclusion Criteria:

• Current weight < 600g

• Neonates under palliative care

• Therapeutic hypothermia for perinatal anoxia

• Neonates who underwent a surgical procedure during the past 72 hours

• Neonates receiving concomitantly a paralytic or another drug for sedation or analgesia other than morphine or midazolam (except for paracetamol/acetaminophen)

• Parents refusing that their child participate

Related Conditions & MeSH terms

• Sedation Complication

Intervention

Other:
• Dose-effect relationship of morphine +/- midazolam administration
Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling

Locations

Country	Name	City	State
France	CHRU Morvan	Brest
France	CH SUd Francilien	Corbeil-Essonnes
France	CHI Créteil	Créteil

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal Creteil

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effective dose for 50% of patients (ED50 ) of morphine in continuous infusion in neonates ventilated in the neonatal intensive care unit	To evaluate which dose is effective, cComfort will be assessed with COMFORTneo score (scale from 6 to 30 with decreasing score with increasing comfort). The dose-response relationship will be assessed with the correlation between a comfortable score (between 11 and 13) and the effective dose for 50% of patients (ED50), by PKPD modeling	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary	Clearance (ml/min/kg) of morphine and midazolam	Morphine and midazolam serum levels (mg/L) will be used to describe clearance by PKPD	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary	Volume of distribution (L/kg) of morphine and midazolam	Morphine and midazolam serum levels (mg/L) will be used to describe volume of distribution by PKPD modeling	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary	Concentration of morphine	Morphine serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary	Concentration of midazolam	midazolam serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary	Doses of morphine and midazolam (µg/kg/h)	PKPD models will be used to simulate doses to determine optimal doses required according to gestational age, postnatal age, corrected age, weight and clinical context	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary	To assess pain responses by the Newborn Infant Parasympathetic Evaluation (NIPE) index	NIPE Index which provides an observer-independent, quantitative assessment of comfort and analgesia based on analysis of heart rate variability. The NIPE Index ranges from 0 to 100 with increasing index with increasing comfort	From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks